Unraveling the connection between PFOA and bladder cancer: A study integrating network toxicology, molecular docking, and experimental validation.

PFOA, an environmental pollutant linked to bladder cancer, has unclear molecular mechanisms. Integrating transcriptomic data with network toxicology and machine learning, we identified 125 shared genes related to PFOA and bladder cancer. Machine learning refined a 16-gene prognostic signature. Molecular docking revealed NUDT1 as the top candidate with strong PFOA binding affinity. Functional experiments showed PFOA upregulates NUDT1, enhancing bladder cancer cell proliferation and migration. NUDT1 knockdown attenuated these malignant effects and partially reversed PFOA's impact. Thus, PFOA promotes bladder cancer progression via NUDT1 interaction, positioning NUDT1 as a potential biomarker and therapeutic target for PFOA-associated carcinogenesis.